In this year we devoted extensive effort to the development of improved force fields that can interface seamlessly with quantum chemical methods, in particular Density Functional Theory, to study the reaction mechanism of the RNASE-H and polymerase active sites of the HIV-1 reverse transcriptase. Due to the high concentration of charged amino acid and nucleic acid residues, as well as the presence of metal ions, the treatment of short ranged and long ranged electrostatics is critical to achieving reliable results. We are currently performing mixed quantum chemical/ clasical simulations of the reaction mechanism of the human pol lambda DNA polymerase ternary complex and the epsilon exonuclease enzyme, which provides the main proofreading functionality for DNA replication in the common E. Coli bacteria. As well as being of fundamental importance in themselves, these systems, being much better characterized structurally (higher resolution) than the corresponding active sites in HIV-1 reverse transcriptase, provide important tests of the quality of our developed methods.